Heparin-like complex carbohydrates activate the esterase inhibitor, antithrombin, and tyrosine hydroxylase from the CNS in a manner that involves multiple modulating interactions. Heparin promotes two activated states in antithrombin: Its major binding site (unique sequence) activates against factor Xa but not thrombin, while binding of this site plus a secondary region (about eight saccharides away) activates the inhibitor against both enzymes. Structure-function relations of newly isolated heparin octa-to-octadecasaccharides along with model sugar units are investigated using intrinsic and extrinsic circular dichroism spectroscopy. A disaccharide sequence is proposed which is the first to elucidate the structure of the second binding region. Conformational basis for multiple regulatory movements in antithrombin are explored by fluorescence and circular dichroism spectroscopy of antithrombin complexes with octa-to- octadecasaccharides and higher molecular weight fractions and by kinetic analysis. These studies provide the first evidence for a conformational difference between the two activated states of antithrombin. Molecular basis of activation of tyrosin hydroxylase by heparin is investigated by in vitro kinetic analysis using partially purified enzyme plus heparin fractions in combination with newly identified peptide inhibitors.